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Multidrug-resistant tuberculosis patients respond poorly to antituberculosis therapy and therefore require new modalities of treatment to overcome the infection. Administration of low dose recombinant human interleukin 2 (rhuIL-2) in combination with chemotherapy to multidrug-resistant tuberculosis patients resulted in reduced or cleared sputum acid-fast bacilli in about 60% of the patients in association with enhanced activation of the immune system. Daily rhuIL-2 administration for 30 days induced increases in CD25+ and CD56+ cells in the blood. rhuIL-2 therapy also resulted in increased expression of gamma-interferon and IL-2 mRNA at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin. Differential display reverse transcriptase PCR revealed several genes expressed at the DTH skin test site that were up- or down-regulated during rhuIL-2 treatment. The differentially regulated genes included components of endocytic vacuoles, enzymes of the respiratory pathway and other regulators of cellular function. The physiological importance of the differential expression of these genes is under investigation to determine their roles in leukocyte activation and in the development of an antimycobacterial response.

We previously demonstrated that although human cytotoxic T lymphocytes (CTL) generated against a lymphoblastoid cell line (LCL) mutant that had lost DR and DQ (formerly known as MB) expression were directed primarily at class I antigens, the lytic activity of such CTL could be inhibited by monoclonal antibodies (MoAb) against monomorphic determinants on DR molecules. Furthermore, the inhibitory effect was found to occur by binding of the MoAb to the target cell, not the effector cell, because lysis of LCL target cells not expressing DR was not inhibited. In this paper we extend this phenomenon to show (i) that MoAbs directed against DQ and DP class II gene products also inhibit the lysis of LCL target cells by CTLs recognizing class I antigens; and (ii) that not all DR-specific MoAbs blocked target cell lysis by non-DR specific CTLs. In addition, when PBLs were used to stimulate the generation of CTLs in mixed leukocyte culture (MLC), inhibition using anti-class II (DR, DQ, and DP) MoAb occurred only when LCLs but not PHA blasts were used as targets. This might be explained by elevated expression of class II molecules on LCLs compared to PHA blasts.

Monoclonal antibodies directed at monomorphic determinants on A,B,C (w6/32) or DR (L243, S4/24, S8/8) HLA antigens were used to inhibit the cytotoxic activity of class I- or class II-reactive CTL clones. Anti-class I (HLA-Bw62) cytotoxic T lymphocyte CTL clones were inhibited by w6/32, but not by L243, when tested on PHA blasts and LCL as targets. Interestingly, S4/24 and S8/8 demonstrated a differential blocking ability of class I reactive clones; these two monoclonal antibodies could not block Bw62-directed CTL clones when using PHA blasts as targets but strongly inhibited the cytotoxic activity of the same clones on LCLs as targets.