CD4+CD45R+ cells are preferentially activated through the CD2 pathway

CD4 cell subsets, CD4+CD45R+ (CDw29-) cells and CD4+CD45R- (CDw29+) cells, can be differently triggered by various stimuli and possess distinct functions. In the present study, cell activation in CD4+CD45R+ and CD4+CD45R- subsets mediated by CD3-Ti antigen-receptor complex or CD2 molecule were examined by using anti-CD3 antibody or pairs of anti-CD2 antibodies (anti-T11(2) and anti-T11(3) antibodies). The results showed that CD4+CD45R+ cells were preferentially activated through the CD2 pathway, whereas both subsets were equally activated through the CD3-Ti antigen-receptor pathway when a second signal such as monocytes or interleukin 2 was present. The different responsiveness of CD4+CD45R+ and CD4+CD45R- subsets through the CD2 molecule did not appear to be due to differences in the distribution or number of T11(2) and T11(3) determinants. These data suggest that some part of the functional diversity of CD4 cell subsets might be explained by the differences in cell activation through the CD2 molecule.     

Immune activation and T cell subset abnormalities in circulation of patients with recently diagnosed type I diabetes mellitus.

The peripheral blood lymphocytes from patients with insulin-dependent diabetes mellitus (IDDM) and healthy controls were analysed for the HLA-DR+, interleukin-2 receptor-positive (IL-2R+) activating antigens, and for CD45R+ and CDw29+ subsets from the purified CD4+ and CD8+ T cells populations. Patients with IDDM had an increased percentage of HLA-DR+ and IL-2R+ cells in both CD4+ and CD8+ T cells. However, the percentage of CD4+ CD45R+ suppressor/inducer T cells were decreased and CD4+ CDw29+ helper/inducer T cells increased in all patients with IDDM, compared with healthy controls. Thus, IDDM patients exhibit a deficiency in the CD4+ CD45R+ suppressor/inducer T cell subsets, which is probably related to the autoimmune phenomenon in this disease. In contrast, the percentage of CD8+ CDw29+ T cell subsets showed no major differences between patients with IDDM and controls. An alteration in the CD4+ CD45R+ and CD4+ CDw29+ T cell subsets appears to be a characteristic feature, and may relate to the impaired cell-mediated immunity in IDDM. These data provide new evidence for T cell dysregulation in IDDM.     

The preferential accumulation of helper-inducer T lymphocytes in inflammatory lesions: evidence for regulation by selective endothelial and homotypic adhesion

The mechanisms which lead to the accumulation of T lymphocytes into inflammatory lesions are not clearly understood. We have previously shown that synovial CD4 T lymphocytes are mostly CDw29+UCHL1+ (helper-inducer cells) and very few carry the CD45R antigen which identifies the suppressor-inducer subset. Synovial CD8+ cells are also CDw29+UCHL1+CD45R-. In the present study, lymphocytes from pleural and peritoneal inflammatory infiltrates were shown to have a similar phenotypic pattern. Furthermore, it was demonstrated that the CDw29+UCHL1+ subset had a greater ability than CD45R+ cells to adhere to endothelial cells and to form homotypic clusters. Differential surface expression of LFA-1 on the two subsets was also shown, but this could not account for the demonstrated adhesion differences. Differences in adhesion between CDw29+/UCHL1+ and CD45R+ cells may explain the preferential accumulation of CDw29+/UCHL1+ cells in inflammatory infiltrates and underlie some of the functional differences between cells taken from sites of chronic inflammation and those from peripheral blood.     

Concomitant augmentation of CD4+ CD45R+ suppressor/inducer subset and diminution of CD4+ CDw29+ helper/inducer subset during rush hyposensitization in hymenoptera venom allergy.

A longitudinal study of patients undergoing rush hyposensitization by honey-bee or yellow jacket venom revealed significant changes of the immunophenotypes until the optimal dose was reached, and a progressive reversion to pre-treatment values in the following months. The activation markers CD23 on B cells and CD25 (IL-2 receptor) on T and B lymphocytes decreased. Although there was little variation of the major CD4 and CD8 lymphocyte populations, CD45R+ cells increased whilst CDw29+ lymphocytes diminished. This inverse variation was associated with a peak of CD4+ CD45R+ cells with concomitant decrease in CD4+ CDw29+ cells showing an inverse effect of the treatment on the reciprocal subsets of CD4 lymphocytes. This indicates a shift in the suppressor/inducer to helper/inducer cell ratio early during rush hyposensitization which may also suggest reversion into a less mature stage of CD4+ cells, associated with the transition from a highly allergen-reactive state to progressive unresponsiveness.     

Selective expression of CD45 isoforms and of maturation antigens during human thymocyte differentiation: observations and hypothesis

Selective expression of high and low molecular weight isoforms of CD45 (T200) occurs coincident with activation of mature T lymphocytes. Expression of CD45 p180 and CDw29 defines antigen-experienced memory T cells in the periphery, and expression of CD45R (CD45 p205/220) defines naive T cells. Upon activation, CD45R+ T cells lose CD45R and acquire CD45 p180 and high density CDw29. In this review we discuss the expression of CD45 isoforms, CDw29, pgp-1 and CD1 on human thymocytes and develop the hypothesis that expression of CD45R marks the generative thymic lineage while expression of CD45 p180 marks those cells destined for intrathymic death. This hypothesis is supported by evidence from phenotypic, molecular and functional analysis of thymocyte subsets. We propose that expression of high molecular weight isoforms of CD45 is essential for growth and differentiation of immature T cells and that inappropriate rearrangement or specificity of TCR activates a transition from expression of CD45R to that of CD45 p180 and intrathymic death.     

Proliferation of human CD4+45R+ and CD4+45R- T helper cells is promoted by both IL-2 and IL-4 while interferon-gamma production is restricted to IL-2 activated CD4+45R- T cells

Recombinant IL-2 (rIL-2) and IL-4 (rIL-4) promote proliferation of human CD4+ T cells activated in the presence of PHA, TPA or OKT-3 monoclonal antibody (MAb), whereas the production of interferon-gamma (IFN) can be induced only by rIL-2. rIL-4 induced strong proliferative responses both in accessory cell independent assays and in the presence of autologous monocytes, but has failed to induce IFN production in any of these systems. The ability of rIL-2 to induce IFN production was strongly enhanced by the addition of monocytes, although a similar proliferative response was recorded in the absence or presence of monocytes. The MAb anti-Tac inhibited the proliferative response and the production of IFN by CD4+ T cells activated in the presence of rIL-2, whereas the proliferative response to rIL-4 was unaffected. CD4+45R+ and CD4+45R- T helper cell subsets proliferated in response to both IL-2 and IL-4. A kinetic analysis demonstrated that the production of IFN throughout a five day activation period was restricted to stimulation of CD4+45R- T cells with rIL-2. This report clearly demonstrates a dissociation of IFN production and T cell proliferation in man. While proliferation can be induced by both IL-2 and IL-4 in both the helper T cell subsets studied, IFN production was induced only in the CD4+45R- subsets and only in response to IL-2.     

Definition of the thymic generative lineage by selective expression of high molecular weight isoforms of CD45 (T200)

Selective expression of CD45 isoforms distinguishes naive and memory T cells in peripheral blood. Paradoxically, although the most recent thymic emigrants are CD45R+ CD45 p180-, the majority of thymocytes are CD45 p180+. Speculating that the small subset of thymocytes selectively expressing only the high molecular weight isoforms of CD45 constitute the thymic generative lineage giving rise to peripheral T cells, we characterized the phenotypic and functional properties of CD45 p180- thymocytes. All cells bearing CD45 p180 were removed by rigorous depletion or all CD45R+ thymocytes were removed in a parallel depletion. CD45R- thymocytes were essentially the same in phenotype and CD4/CD8 subset distribution as unfractionated thymus, and dissimilar to naive peripheral blood lymphocyte (PBL) T cells. In contrast, CD45 p180- thymocytes, mainly CD45R+, were CD1- CD38- pgp 1+, corresponding closely to the phenotype of naive CD45R+ PBL T cells. This subset is enriched in CD4+ or CD8+ single positives, includes a high proportion of CD4-8- thymocytes which are predominantly CD3-, and appears to have a medullary location. Approximately 40%-50% of CD45 p180- thymocytes expressed a high density of CDw29 (4B4), which in the periphery is expressed at high density only on CD45 p180+ memory T cells and at low density on CD45R+ naive T cells. However, the expression of high density CDw29 in the absence of CD45 p180 indicates a close resemblance to fetal lymphocytes and suggests an essential role for CDw29 in both the least and the most mature of T cells. If CD45 p180- thymocytes constitute the generative lineage and CD45 p180+ cells are commited to intrathymic death, then the CD45 p180- subset should have enhanced proliferative potential. By combining depletion methods with a limiting dilution assay for clonogenic potential, we found that 100% of the clonogenic precursors present in unfractionated thymus were CD45R+ CD45 p180- cells. This indicates that the CD45 p180+ majority of thymocytes has a very limited capability for proliferation consistent with a commitment to intrathymic death. The clonogenic potential of CD45 p180- thymocytes indicates a greater functional resemblance to PBL T cells than to CD45 p180+ thymocytes. In so far as clonogenic potential in vitro reflects generative potential in vivo, expression of high molecular weight CD45 isoforms appears to define the generative thymic lineage. Our working hypothesis proposes that expression of CD45 p180 implements the mechanism for eliminating thymocytes with self-reactive receptor specificities.     

Immunoregulatory CD4+ CD45R+ suppressor/inducer T lymphocyte subsets and impaired cell-mediated immunity in patients with Down''s syndrome.

The monoclonal antibodies 2H4 and 4B4 allow CD4+ and CD8+ T lymphocytes to be subdivided into CD45R+ and CDW29+ functional subpopulations. The CD4+ CD45R+ lymphocytes are designated as suppressor/inducer and CD4+ CDW29+ as helper/inducer subsets. Peripheral blood lymphocytes from 19 patients with Down's syndrome and 19 age- and sex-matched normal controls were analysed for the CD45R+ and CDW29+ subsets from the CD4+ and CD8+ T lymphocytes. The percentage of CD4+ CD45R+ cells (suppressor inducer) was markedly increased and of CD4+ CDW29+ cells (helper/inducer) decreased in all patients with Down's syndrome. In contract, the percentage of CD8+ CD45R+ and CD8+ CDW29+ subsets showed no major differences between patients with Down's syndrome and normal controls. Moreover, an alteration in the CD4+ and CD45R+ and CD4+ CDW29+ T cell subsets was accompanied by a markedly reduced proliferative response to phytohaemagglutinin and concanavalin A stimulation of the CD4+ T lymphocytes. Thus, a deficiency exists in patients with Down's syndrome in the CD4+ CDW29+ helper/inducer T cell subset which may contribute to their impaired cell-mediated immunity.     

Increased frequencies of the CD29 and CD57 markers and decreased frequency of CD45RA within CD4+ and CD8+ subsets after allogeneic bone marrow transplantation in man.

Two monoclonal antibodies, anti-CD45RA and anti-CD29, reciprocally divide the CD4+ and CD8+ lymphocytes into CD4+ CD45RA+, CD4+ CD29+, CD8+ CD45RA+ and CD8+ CD29+ subsets. The CD4+ CD45RA+, CD4+ CD29+ and CD8+ CD45RA+ possess suppressor-inducer, helper-inducer and suppressor-effector functions respectively. Since the role of these subsets has not been established after allogenic bone marrow transplantation we studied lymphocyte subpopulations in 12 patients 45-227 days after the procedure. The fraction of CD4+ lymphocytes was significantly (P = 0.0005) decreased to 20 +/- 9% versus 43 +/- 3% in controls. Within the CD4+ compartment, we found an increase in the fraction of CD4+ cells that co-expressed CD29 (CD29+/CD4+) to 92 +/- 10% versus 48 +/- 15% (P = 0.008) in controls and a concomitant decrease in CD45RA+/CD4+ to 16 +/- 12% versus 56 +/- 25% (P = 0.008). Patients were also noted to have an increase in the percentage of CD8+ lymphocytes to 41 +/- 5% compared to 23 +/- 4% in controls (P = 0.0004). Examination of the CD8+ subsets revealed a significant increase in the CD29+/CD8+ fraction to 97 +/- 3% versus 64 +/- 2% in controls (P = 0.008) and a decrease in the CD45RA+/CD8+ fraction to 36 +/- 11% versus 70 +/- 21% (P = 0.008). The number of cells co-expressing CD57 were also determined within the CD4+ and CD8+ subsets. In patients CD57+/CD4+ were increased to 29 +/- 7% versus 1 +/- 1% in controls (P = 0.04), and CD57+/CD8+ to 49 +/- 12% versus 23 +/- 9% (P = 0.02). Since CD29+ and CD57+ cells have a poor capability for IL-2 production and proliferation this shift in subset distribution may account for some of the defects in cellular immunity seen within the first year after allogeneic bone marrow transplantation.     

Deficiency of suppressor-inducer (CD4+CD45RA+) T cells in autism

CD4+ cells are a heterogenous population of lymphocytes including at least two distinct subpopulations: CD45RA+ cells, inducers of suppressor T cells and CDw29+ cells, inducers of helper function for antibody production. To investigate the possibility that immune abnormalities in autism may involve abnormal distribution of these helper subpopulations, monoclonal antibodies were used in flow cytometric analysis to characterize peripheral blood lymphocytes of 36 subjects with autism. The autistic subjects as compared to a group of 35 healthy age-matched subjects had a significantly reduced number of lymphocytes, a decreased number of CD2+ T cells and reduced numbers of CD4+ and CD4+CD45RA+ lymphocytes. The numbers of B (CD20+) cells, suppressor T (CD8+) cells, inducers of helper function (CD4+CDw29+) and natural killer (CD56+) cells were not altered in the autistic subjects. Our results suggest that an alteration in the suppressor-inducer T-cell subset is associated with autism.     

CD8+ T-cell subsets defined by expression of CD45 isoforms differ in their capacity to produce IL-2, IFN-gamma and TNF-beta.

Expression of different isoforms of CD45, the leucocyte common antigen (LCA), on T-cell subsets has permitted distinctions between the functional activities of subpopulations within the major CD4+ T-cell subset. With respect to cytokine production, the expression on CD4+ cells of CD45RA, a high molecular weight isoform, defines a population which produces only interleukin-2 (IL-2) and tumour necrosis factor-beta (TNF-beta) in quantity, with peak production of IL-2 occurring after 24-48 hr stimulation, while the CD4+ population bearing high levels of CD45RO, a low molecular weight isoform, can produce a wide range of cytokines within 24 hr of activation. The literature is conflicting on the capacities for cytokine production of CD8+ subsets divided on the basis of either CD45RA or CD45RO expression. The aim of this study was to attempt to clarify this area by determining the amount and kinetics of production of IL-2, interferon-gamma (IFN-gamma) and TNF-beta in CD8+ cells separated on the basis of both CD45RA and CD45RO isoform expression. The results showed that CD8+ CD45RA- and CD8+ CD45RO+ T lymphocytes produce significantly more of all three cytokines than do CD8+ CD45RA+ or CD8+ CD45RO- T cells. The kinetics for IFN-gamma and TNF-beta production were similar for both subsets, while IL-2 production was delayed by approximately 3 hr in the CD8+ CD45RO- population as compared to the CD8+ CD45RO+ subset. It is suggested that some of the confusion over cytokine production by these CD8+ subsets may be attributable to different conditions for isolation causing pre-activation of positively selected populations. It is also suggested that while CD8+ CD45RA+ cells are shown to acquire CD45RO upon activation, as do CD4+ CD45RA+ cells, the results of the present study argue for a different relationship between CD8+ subsets separated on the basis of CD45 isoform expression than between the corresponding CD4+ subsets.     

Age-related changes in naive and memory CD4+ T cells in healthy human children

Subsets of CD4+ T cells originally identified functionally as suppressor-inducer and helper-inducer populations have recently been reinterpreted as naive and memory maturational states. The subsets can be identified by the surface expression of CD45R and CDw29, respectively. Using two-color flow cytometric analysis, we measured these CD4+ T cell subsets in two samples of cord blood and in 26 healthy children between the ages of 1 and 19 years. As has been reported by others, we observed that the majority of CD4+ T cells in cord blood consist predominantly of the CD45R+ subset. With aging we could demonstrate a gradual acquisition of CDw29+, CD4+ T cells and a concomitant gradual decrease in the percentage of CD45R+, CD4+ T cells. These age-related changes are consistent with the concept of naive (CD45R+) and memory (CDw29+) subsets. Further, because of the dynamic changes, their utilization as prognostic indicators in immunologic disease states cannot be applied to children in the same manner as adults.     

CD45R CD4 T cell subset-reconstituted nude rats: subset-dependent survival of recipients and bi-directional isoform switching.

High and low molecular weight variants (CD45R) of the leukocyte common antigen (CD45) divide CD4 T helper cells into subpopulations which display distinct characteristics. In vitro and in vivo evidence suggested that the presence of the high molecular weight splice variants CD45RA or CD45RB distinguished naive CD4 T cells from memory T cells which underwent an irreversible switch to the low molecular weight isoform as a consequence of antigen encounter. In the rat monoclonal antibody MRC OX22 identifies an epitope on the CD45RB molecule. We investigated this proposed differentiation pathway by reconstituting athymic nude rats with highly purified OX22+ or OX22- CD4 T lymphocyte subsets obtained from the thoracic duct (TDL) of euthymic, congenic, allotype-marked donors. Injection of CD4+CD45RB- (45R-) cells ensured long-term survival of nude recipients; recipients of CD4+CD45R+ (45R+) cells died within 2-3 months of injection. Early after transfer (3-4 weeks) the progeny of both 45R+ and 45R- TDL were uniformly 45R-. With time (by 2 months) progeny of both parental types expressed the high molecular weight CD45RB isoform. Nude recipients of 45R- TDL always generated progeny a proportion of which bore the 45R+ phenotype; 3 months to 2 years post-injection, 30%-50% of the donor-derived CD4 T cells were 45R+, 45R- progeny isolated from primary recipients of either 45R- or 45R+ cells transferred into secondary nude recipients induced skin allograft rejection with equal effectiveness and also generated 45R+ offspring. The results indicated that CD4 T cell subsets switched between CD45R isoforms and that the change between high and low molecular weight expression was bi-directional. The splice variants apparently are not lineage or maturation markers, but rather identify CD4 T cells that exist transiently in different functional states.     

Peripheral blood mononuclear cell abnormalities and their relationship to clinical course in homosexual men with HIV infection

Quantitative abnormalities of leukocyte subpopulations have been shown to correlate with clinical status in human immunodeficiency virus (HIV) infection. We have performed peripheral blood leukocyte phenotyping in 23 HIV-seropositive homosexual men, and correlated the results with clinical follow-up information. Individuals with CD4+ greater than 400/mm3 (Group 1) had less severe abnormalities in other mononuclear cell subpopulations than patients with CD4+ less than 400/mm3 (Group 2). Group 1 had decreased CD4+CDw29+ (B-cell inducer) cells, compared to HIV-seronegative homosexual controls, with normal CD4+CD45R+ (suppressor-inducer) cells, suggesting that CD4+ subpopulations are reduced at different rates. Group 2 had decreased counts for both CD4+CDw29+ and CD4+CD45R+ cells. Both groups had increased cytotoxic T cells (CD8+CD11b-), with decreased B cells and CD4+/CD8+ ratios, compared to HIV-seronegative homosexual controls. The Group 2 patients with subsequent clinical deterioration had particularly low CD4+ cells, CD4+CD45R+ cells, CD2+Ta1+ cells, and CD4+/CD8+ ratios and high CD8+CD11b- cells, compared to those with clinically stable illness. Our findings suggest that specific leukocyte subpopulations are altered differentially at various stages of HIV infection. However, the study involved only quantitative measurements of specific T- and B-cell subsets with no attempt to measure in vitro function. It is of course possible that normal numbers of cells in these subpopulations might be functionally deficient.     

Lymphokine gene expression related to CD4 T cell subset (CD45R/CDw29) phenotype conversion

In this study, we investigated whether the phenotype-related differentiation of human 2H4+ (CD45R) naive cells to 2H4- (CDw29) memory CD4 cells corresponded to modulation of interleukin (IL) 2, IL 4, interferon (IFN)-gamma and granulocyte-monocyte colony-stimulating factor (GM-CSF) gene expression, a phenomenon which might correlate to the distinct functional activities of naive cells or memory cells. To mimic in vitro CD4 T cell subset differentiation, freshly isolated 2H4+ and 2H4- CD4 cells were stimulated with the anti-CD3 antibody (Leu-4), expanded in IL 2-containing medium and restimulated with Leu-4 after 7 and 13 days. Absence of monocyte-T cell interaction was compensated by adding monocyte supernatant to the culture medium and by cross-linking the anti-CD3 antibodies with goat anti-mouse antibody coated on culture dishes. It has been previously shown that in vitro stimulated 2H4+ cells acquire CDw29 surface antigens. Measurement of lymphokine gene expression by dot-blot hybridization revealed that although stimulated 2H4+ cells proliferated less than stimulated 2H4- cells, and expressed less actin mRNA, they expressed more IL 2 but less IL 4 and GM-CSF than 2H4- cells. No significant difference was observed between the two subsets for the expression of IFN-gamma. If subsets were restimulated with Leu-4 antibodies, expression of IL 2 was decreased and expression of IL 4 was increased in both subsets; however, the differences among the subsets persisted. They were even more enhanced for IL 2 but less pronounced for GM-CSF. Thus, in spite of phenotype conversion, CD4 T cell subsets maintained a distinct capacity to express IL 2 and IL 4 genes.     

Sex difference in the CD4 + CD45R+ T lymphocytes in normal individuals and its selective decrease in women with idiopathic thrombocytopenic purpura

Chronic idiopathic thrombocytopenic purpura (ITP) is a well-defined autoimmune hematologic disorder. It is more common in women than men. We have shown that patients with active disease have abnormal T cell subsets which are more perturbed in women than in men and functional abnormalities that are confined to the T lymphocytes. In the current study, the anti-2H4 (CD45R) monoclonal antibody was used to divide the CD4 subset into their CD4+ CD45R+ and CD4+ CD45R- T lymphocytes. The subpopulations were measured in the peripheral blood of 26 women and 15 men with active ITP, 16 women and 8 men with disease in remission, and 33 normal healthy women and men. Normal women had increased percentages (P less than 0.0001) and numbers (P less than 0.005) of the CD4+ CD45R+ lymphocytes compared to normal men. Women with active disease had reduced percentages and numbers of CD4+ CD45R+ lymphocytes compared to normal women (P less than 0.0001) and women with disease in remission (P less than 0.001). Those women with decreased CD4+ CD45R+ lymphocytes had a significantly depressed lymphocyte response to polyclonal T cell mitogens. In contrast, men with active disease had neither such phenotypic changes nor functional correlations. The percentages and numbers of CD4+ CD45R- lymphocytes were not changed in either sex with active disease. In conclusion, women, but not men, with active ITP appear to possess a reduced subpopulation of CD4+ CD45R+ T lymphocytes.     

Human CD8+ intraepithelial T lymphocytes are mainly CD45RA-RB+ and show increased co-expression of CD45R0 in celiac disease

Expression of various CD45 isoforms (RA, RB and R0) on CD3+, CD4+ and CD8+ intraepithelial and lamina propria T cells was examined in situ by a three-color immunofluorescence technique in jejunal biopsy specimens from 32 patients with celiac disease and 18 controls. The median percentage of CD3+ intraepithelial lymphocytes (IEL) that expressed CD45R0 increased from 52% in controls to 69% in untreated celiac disease (p less than 0.01). Furthermore, the percentages of CD4+ and CD8+ IEL strongly positive for CD45R0 rose respectively from 94% and 24% in controls to 100% and 55% in untreated celiac disease. Conversely, CD45R0 was strongly expressed on most CD3+ lamina propria lymphocytes (LPL) both in control (81%) and diseased (77%-81%) mucosa. A variable fraction of the intraepithelial and lamina propria CD3+ T cells expressed mainly CD45RB (controls, 46% and 20%, respectively; celiac disease, 29% and 15%). Only 2% IEL and 4% LPL were positive for CD45RA. Expression of different CD45R isoforms thus identified three distinct CD8+ T cell subsets in human intestinal mucosa. In addition, our results suggested that antigen-primed CD8+CD45R0+ memory cells accumulate in the jejunal epithelium of patients with untreated celiac disease.     

Concomitant augmentation of CD4+ CD29+ helper inducer and diminution of CD4+ CD45RA+ suppressor inducer subset in patients infected with human T cell lymphotropic virus types I or II.

To examine the immunomodulatory effects of HTLV infection, lymphocyte subset analysis was performed on patients infected with human T cell lymphotropic virus type-I (HTLV-I, n = 6) or -II (HTLV-II, n = 12) and on normal blood donors (n = 16). The percentages of total B lymphocytes (CD19), natural killer (NK) cells (CD16), T lymphocytes and their subsets (CD2, CD3, CD4, CD5, CD7, CD8), and IL-2R (CD25) were found to be within the range found in normal donors. However, the expression of CD8+ HLA-DR+ increased significantly in patients with HTLV-I or HTLV-II infection (14.1 +/- 3.9% and 9.7 +/- 2.4% respectively; P less than 0.01) when compared with controls (3.2 +/- 1.1%). In addition, there was a significantly greater proportion of CD4+CD29+ T lymphocytes (29.3 +/- 6.1% and 31.1 +/- 9.0%; P less than 0.05) with concomitant diminution of CD4+CD45RA+ T lymphocytes (8.3 +/- 3.3% and 11.4 +/- 1.5%; P less than 0.01) in patients infected with HTLV-I or HTLV-II respectively, when compared with controls. The increased percentage of CD4+CD29+ subpopulations showed a direct correlation (rs = 0.86; P less than 0.001) with HTLV-specific antibody production. No difference in the CD8 population coexpressing CD29 and S6F1 (an epitope of LFA-1) were observed in the HTLV-infected group when compared with normal donors and functional analysis exhibited minimal cytotoxicity against lectin labelled heterologous target cells. Thus, the shift in the suppressor/cytotoxic to helper/inducer 'memory' CD4+ may be associated with immunoregulatory abnormalities often found in persons infected with HTLV-I or HTLV-II.     

Selective loss of CD4+ CD45R+ T cells in peripheral blood of multiple myeloma patients

The phenotypic distribution of T-lymphocyte subsets in peripheral blood from multiple myeloma (MM) patients shows a reduced proportion of CD4+ cells and a normal proportion of CD8+ cells. The decrease in CD4+ cells could be due to a random process, with all types of CD4+ cells being equally affected, or it could reflect a nonrandom process with selected subsets preferentially reduced. In order to distinguish between these possibilities, double immunofluorescence analysis was performed on blood samples from patients with MM, patients with monoclonal gammopathy of unknown significance (MGUS), and age-matched normal donors, using monoclonal anti-CD4 or anti-CD8 paired with antibodies to the common leukocyte marker Lp220 (CD45R) or 4B4 (CDw29). Normal peripheral blood lymphocytes (PBL) include two phenotypically and functionally distinct CD4+-cell subsets, identified as CD4+ Lp220+ 4B4-and CD4+ Lp220- 4B4+, whereas the majority of CD8+ cells expresses Lp220 (70–85%). MM patients had a highly significant selective reduction of the CD4+ Lp220+ subset compared with normal controls (P<0.001). Although the percentage of CD4+ Lp220- cells was also reduced in some MM patients relative to normal donors, most of MM patients had an elevated Lp220-/Lp220+ ratio of CD4+ cells (P<0.001). The proportion of the two CD8+ subsets was also markedly abnormal. In the set of patients studied the abnormalities within the CD4+ and CD8+ lymphocytes were exclusive to patients with MM since patients with MGUS had normal proportion of CD4+ and CD8+ subsets.