Maureen Cassin

Extracorporeal photochemotherapy does not suppress T- or B-cell responses to novel or recall antigens.

BACKGROUND Extracorporeal photopheresis (ExP) is an effective therapy for several conditions including cutaneous T-cell lymphoma, scleroderma, and allograft rejection. Experimental animal models suggest that ExP may induce antigen-specific immunosuppression. OBJECTIVE Our purpose was to determine the effect of photopheresis on humoral and cell-mediated immunity in human subjects. METHODS Recall and primary immune responses of patients with scleroderma receiving monthly ExP treatments were assessed by delayed type hypersensitivity skin tests, T-cell proliferative responses after immunizations with tetanus toxoid and keyhole limpet hemocyanin, and serum antibody titers against common viral pathogens. RESULTS After 6 months of ExP, viral antibody titers and delayed type hypersensitivity responses were not significantly different from baseline values in all 7 patients tested. T-cell responses to tetanus toxoid remained normal in 3 of 3 patients tested for a minimum of 6 months after booster immunization. Immunization with the protein antigen keyhole limpet hemocyanin after initiation of ExP therapy resulted in sustained T-cell proliferative responses up to 6 months in 3 of 3 patients. CONCLUSION These results, along with the observation of no increased incidence of opportunistic infections or neoplasms, suggest that ExP is not broadly immunosuppressive and does not prevent primary responses to vaccination or other antigenic challenges.

The potential therapeutic role of interleukin-12 in cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a lymphoproliferative disorder characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature T-helper (Th) cells. Sezary syndrome (SzS) represents an advanced form of CTCL associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by peripheral blood mononuclear cells (PBMCs) in SzS characterized by increased IL-4 and deficient IL-2 and IFN-gamma production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, indicating that the clonal T-cell population is likely derived from the T-helper type 2 (Th2) subset of helper T lymphocytes. Furthermore, a variety of immune abnormalities have been observed in association with SzS that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-gamma production and causes the activation of cytotoxic lymphocytes, we assessed the production of IL-12 by PBMCs from SzS patients, and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and, thus, possibly lead to correction of immune defects. In this review, we present our data, which indicate that patients with SzS exhibit marked defects in monocyte production of IL-12 p70. Moreover, in vitro culture of PBMC from SzS patients with recombinant IL-12 leads to reconstitution of normal IFN-gamma production and markedly enhances cell-mediated cytotoxicity.

Expression of interleukin-4 and interleukin-5 mRNA in developing cutaneous late-phase reactions

The stimuli for the accumulation and activation of eosinophils, which are prominent components of IgE-mediated allergic late-phase reactions (LPRs), are not defined. Messenger RNA for interleukin-5 has been found in lymphocytes present in biopsy specimens of skin obtained during LPR 24 hours after antigen challenge. However, it is not known whether interleukin-5 is present to attract or activate the eosinophils that accumulate during the first 6 hours after antigen challenge when cutaneous LPRs are developing. Using reverse transcription-polymerase chain reaction, we have found mRNA for interleukin-5 in biopsy specimens obtained from control challenge sites nor in specimens from sites of antigen challenge of nonreactive subjects. We also found mRNA for interleukin-4 in these sites developing LPR. This pattern suggests that these cytokines may be important in eosinophil accumulation and activation during developing LPR. These findings are of considerable clinical relevance because the eosinophils in LPR are postulated to play major pathogenic roles in chronic allergic diseases.