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The major histocompatibility complex (MHC) class II deficiency syndrome is a rare immunodeficiency disease associated with defective expression of class II MHC antigens. We have examined the consequences of this defect for the differentiation and functional capabilities of immunoregulatory T-cell subpopulations in an affected patient. Although the number of circulating T cells was normal, there was a striking reduction in the number of CD4+ T cells. Furthermore, purified CD4+ cells from the patient were unable to provide help for antibody secretion. This defect in helper function appeared to be due to the abnormal differentiation of the few CD4+ cells present, virtually all of which expressed the CD4 + HB11 + phenotype characteristic of immature “virgin” T cells. Abnormal development of immunoregulatory CD8+ T cells was also observed. Although increased numbers of CD8+ T cells were present, virtually none had phenotypic properties of suppressor cells (i.e., CD3+/CD8+/9.3-granular lymphocytes that coexpress the Leu-15 or Leu-7 antigens), and purified CD8+ cells from the patient had no suppressor activity. Thus, the absence of class II MHC antigens profoundly disrupts the development of immunoregulatory T cells. We propose that these effects occur by the following mechanisms: (1) the absence of intrathymic class II antigens results in deficient production of CD4+ cells, (2) the CD4+ cells that do emerge from the thymus do not undergo postthymic maturation into CD4+HB11- cells with helper capabilities, and (3) the absence of CD4+HB11- effector cells results in abortive development of suppressor cells involved in feedback suppression.

Serial measurement ofin vitro immunologic parameters in patients is used to detect change in immune status over time due to disease progression and/or immunodulatory therapy. A statistical method is presented for looking at serial measurements on an individual to detect whether a change in a parameter is outside the bounds of expected within-individual variation. Analysis of variance is used, assuming a normal distribution, to obtain percentiles of the distribution of the absolute difference between consecutive values of immunologic parameters in a healthy population. The assumptions in this analysis are justified from a statistical point of view. We discuss how to use this statistical method to make judgments relevant to clinical immunology, including (1) how to construct a table that can be used to determine quickly if an “interesting” change for some standard immunologic parameters has occurred, (2) whether a linear (additive) or logarithmic (proportional) model for change might be more appropriate for a given parameter, and (3) how to modify the calculations if change is expected in a certain direction or if multiple pre- and/or postevent (clinical change or intervention) measurements are available.

Testing of cytotoxic function using a panel of natural killer (NK)-sensitive target cells, including a unique herpes simplex virus-infected Raji-cell target, was performed in conjunction with phenotypic cell analysis by dual-color flow cytometry to characterize the NK system. Subjects included in the study were at risk for or infected with the etiologic agent of the acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV). A generalized defect in NK function was temporally correlated with disease manifestations, as evidenced by deficient NK lytic function in patients with AIDS and AIDS-related complex (ARC). Healthy at-risk subjects, including those seropositive for HIV, exhibited robust NK-cell function. Phenotypic analysis revealed that normal proportions of the NK-associated CD16+ (Leu11) Leu7− and CD16+(Leu11)Leu7+ lymphocyte subsets were maintained throughout the clinical progression of HIV infection. However, the proportion and numbers of cells of the CD8+(Leu2)Leu7+ subset were increased in AIDS, ARC, and healthy at-risk subjects, including those seronegative for HIV. These results are consistent with a qualitative defect in the NK system in AIDS, perhaps secondary to CD4-cell depletion and a concomitant lack of essential accessory factors. The elevation in CD8+(Leu2)/Leu7+ cells is not solely the result of HIV infection and may be a general response to viruses and/or other antigenic stimulation.