Site of action of serum factors that block delayed-type hypersensitivity in mice.

Abstract

Delayed-type hypersensitivity (DTH) 1 develops without adjuvant if the dose of SRBC given is appropriate to the route of inoculation (1). Increasing the amount of antigen reduces and eventually abolishes all evidence of DTH. Animals blocked by an excessive dose of SRBC cannot be subsequently sensitized, even when an optimal dose of antigen is given subcutaneously, the most reliable route for inducing DTH in the mouse. DTH does develop, however, when a massive intravenous dose of antigen is given to splenectomized mice, or mice that have received cyclophosphamide before immunization (2). The suppression of DTH cannot therefore be due to excess antigen, as such. The serum of DTH-suppressed mice will partially inhibit the induction and expression of DTH in normal recipients, an effect which is substantially increased by partial absorption of the serum with specific antigen (3). In contrast to a high dose of antigen (4), absorbed serum does not inhibit the proliferative response or the formation of plaque-forming cells (PFC) in lymph nodes draining the site of antigen injection. Moreover, the specific antibody titer is increased by absorbed blocking serum even though the induction of DTH is totally suppressed by it.In light of indications that the products of the interaction between antigen and antibody depress the activated T cells which mediate DTH, and insofar as pretreatment with specific IGM antibody has been reported to enhance the antibody response (5, 6), an important question arises concerning the functional relationship between the mediators of DTH and the T cells responsible for helper activity in the antibody response. Obviously, a successful antibody response depends upon cooperation between the various cellular and humoral elements involved (7). It is possible that this can be accomplished efficiently only in certain sites, and that the local enactment of a DTH reaction is the process whereby the participating elements are assembled (8). After intravenous immunization, the spleen could be the locus of this coordinated series of events. Evidence in support of this concept is presented in the present report,

Relationships between radiological pattern and cell-mediated immune response in Mycoplasma pneumoniae pneumonia

“…TSUNEKAWA et al [7] reported that in PPD-negative MP patients the number of peripheral blood T-lymphocytes was not significantly lower, but blastogenic lymphocyte response to PPD and PPDinduced IFN-γ production were significantly reduced compared with PPD-positive patients. LAGRANGE et al [19] suggested that cutaneous tuberculin anergy could result if the number or activity of circulating committed T-cells was depressed, and cutaneous anergy has been demonstrated to result from circulating suppressor cell. Previous data support the role of the suppressor cells, monocytes or macrophages in impairing CMI reactivity and delayed hypersensitivity to PPD at sites distant from the active focus, without inhibiting the appropriate response in the area of inflammation [15,20].…”

The negative tuberculin test. Tuberculin, HIV, and anergy panels.

“…In that type of anergy, as in sarcoidosis, reactivity can be restored by concurrent administration of hydrocortisone (179). Antigen-specific depression of reactivity to tuberculin can be induced in mice by administration of high doses of mycobacterial antigens (217). In another study, however, injection of mice with BCG caused depression of unrelated DTH reactivity in mice (218).…”

“…The technical factors that cause erroneous interpretations of tuberculin tests may have a role in falsely negative tuberculin tests in clinical settings (124,254,255). Mackaness suggested that cutaneous anergy could result if the number or activity of circulating committed T-cells was depressed (217,231). If this happens, the response to antigen at clinically irrelevant sites could be impaired, whereas that at the site of inflammation may be normal.…”

“…This concept was expanded by other investigators who demonstrated that cutaneous anergy can result from circulating suppressor cells, which depress the reactivity of circulating cells. Such cutaneous anergy does not reflect the antimicrobial status of the immune system (162,217,221,224,231,243). Mycobacterial products have been shown to depress cellular immune reactivity, specifically to tuberculin (70,223,256).…”

“…There is ample documentation in clinical material and in animal experiments to support the assumption that delayed hypersensitivity, although closely linked with antimicrobial cellular immune functions, can be separated from true cellular immunity (93,160,217,257,258). In the Lubeck vaccination disaster, in which 251 infants received virulent M. tuberculosis instead of the intended BCG, it was noted that nine of the 174 who survived (six children had no symptoms suggestive of tuberculosis) were repeatedly tUberculin-negative (259).…”